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Viruses and cytokines: Evidence for multiple roles in pancreatic beta cell destruction in type 1 insulin‐dependent diabetes mellitus
Author(s) -
Campbell Iain L.,
Harrison Leonard C.
Publication year - 1989
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240400107
Subject(s) - beta cell , tumor necrosis factor alpha , biology , major histocompatibility complex , pancreatic islets , insulin , immunology , beta (programming language) , cytokine , mhc class i , cell , interferon gamma , endocrinology , immune system , islet , biochemistry , computer science , programming language
Insulin‐dependent (type 1) diabetes mellitus (IDDM) is due to the selective autoimmune‐mediated destruction of pancreatic beta cells possibly initiated by viruses. To elucidate the possible role of viruses and cytokines in the pathogenesis of IDDM, we have examined the effect of reovirus infection on beta cell major histocompatibility complex (MHC) expression and the effect of interferon‐γ (IFN‐γ) and tumour necrosis factor‐α (TNF‐α) on beta cell function in vitro. Infection of RIN‐m5F (rat insulinoma) cells with reovirus‐1 or reovirus‐3 was associated with a tenfold increase in class 1 MHC protein and mRNA expression. Reovirus infection did not induce the expression of class 11 MHC by RIN‐m5F cells. Exposure of reovirus to ultraviolet light almost completely abolished its ability to induce class 1 MHC protein expression on infected cells. Murine islets cultured for 3 days with IFN‐γ and/or TNF‐α had a significantly reduced insulin response to glucose, which was more marked with a combination of the cytokines. During 6 days of culture in IFN‐γ plus TNF‐α islets underwent noticeable degeneration associated with an 80% reduction in insulin content. These findings together with previous data suggest viruses and cytokines may have multiple roles in beta cell destruction, indirectly through enhanced MHC protein expression and directly through functional impairment and loss of viability.